Preclinical Profile of CM699 as a Medication Candidate for Stimulant Use Disorder.

ABSTRACT: There currently are no medications proven to be effective for the treatment of stimulant-use disorder (SUD). Sigma-receptor (σR) antagonists block many effects of stimulant drugs but not the reinforcing effects assessed with self-administration in rats. However, a recent study suggests that σR antagonism combined with a dopamine (DA) transporter (DAT) blockade selectively attenuates stimulant self-administration. A compound with potential for dual DAT/σR inhibition, CM699, was synthesized and had the necessary ex vivo affinities of 311 and 14.1 nM at DAT and σ₁Rs, respectively. CM699 inhibited DA uptake ex vivo. Antagonist effects at σ₁Rs by CM699 were confirmed with a recently reported pharmacological assay: CM699 increased, whereas the σ₁R a

SUBMITTER: Hiranita T 

PROVIDER: S-EPMC12408108 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature